This proposal describes a training program for the development of an academic career in hematopoietic stem cell (HSC) transplantation. The principal investigator (PI) is a junior faculty of the Bone Marrow Transplant Program at H. Lee Moffitt Cancer Center. The PI will expand her scientific skills through training as participant of a Physician-Scientist mentorship program. Dr. Claudio Anasetti, Chief of the Bone Marrow Transplantation Program and an authority in hematopoietic cell transplantation, will mentor the principal investigator's scientific development. In addition, an advisory committee of highly regarded medical scientists will provide scientific and career advice. Prolonged thrombocytopenia after high dose chemotherapy is a problem associated with increased morbidity and mortality. The proposed research will provide preclinical data on novel strategies to improve platelet reconstitution post transplant. Dr. Perez proposes to study the thrombopoietic role of in vitro generated megakaryocytes in a xenotransplantation model for human megakaryocytopoiesis. In vivo approaches to improve their function with chemokines and/or accessory cells will be studied. Research on apoptotic mechanism affecting engraftment of cycling HSC that may translate on improved homing, engraftment and differentiation of in vitro cytokine stimulated HSC to generate megakaryocytes will be addressed. In addition, molecular studies of genes that may regulate megakaryocytopoiesis and participate in platelet recontitution will be studied. Moffitt Cancer Center has an extremely nurturing environment and provides an ideal setting for training physician scientists. Interactions between scientists, physician/scientists and clinical investigators maximizes the potential of the PI to establish a successful independent research program on hematopoietic stem cell biology and transplantation.